Hepatitis C virus (HCV) is an important cause of chronic liver disease in the United States and a continuing regulatory challenge for ensuring the safety of the blood supply. The Miyazaki Cohort Study is an ongoing study of 973 people in an area of Japan where both HCV and the human T lymphotropic virus type I (HTLV-I) are highly prevalent. Between 1985-1995, there were 14 seroconverters to antibody to HCV (anti-HCV) in this population (3.6 seroconverters per 1,000 person-years in previously seronegative persons). HCV-RNA was detectable in 10 of the seroconverters, and it remained detectable for greater than one year in eight of them. Both HCV and the hepatitis B virus may lead to the development of hepatocellular carcinoma (HCC) in some patients, often in association with mutations in the p53 tumor suppressor gene. Detection of mutations by direct sequencing provides more information than immunohistochemical (IH) staining, but the equipment needed and the time required make it less practical for use in large-scale studies or in studies in developing countries. In a study of 28 HCCs, 19 (68%) had 50 to 95% of cells stained. Mutations in p53 exons 5-8 were found by direct sequencing in 17 (61%), indicating a high level of sensitivity and specificity of IH compared to direct sequencing to detect mutant p53 in HBV-infected patients with HCC.